Farooq Amjad
Department of Biochemistry & Molecular Biology, Leonard Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Curr Top Med Chem. 2015;15(14):1372-84. doi: 10.2174/1568026615666150413154841.
Estrogen receptors, comprised of ERα and ERβ isoforms in mammals, act as ligandmodulated transcription factors and orchestrate a plethora of cellular functions from sexual development and reproduction to metabolic homeostasis. Herein, I revisit the structural basis of the binding of ERα to DNA and estradiol in light of the recent discoveries and emerging trends in the field of nuclear receptors. A particular emphasis of this review is on the chemical and structural diversity of an everincreasing repertoire of physiological, environmental and synthetic ligands of estrogen receptors that ultimately modulate their interactions with cognate DNA located within the promoters of estrogenresponsive genes. In particular, modulation of estrogen receptors by small molecule ligands represents an important therapeutic goal toward the treatment of a wide variety of human pathologies including breast cancer, cardiovascular disease, osteoporosis and obesity. Collectively, this article provides an overview of a wide array of small organic and inorganic molecules that can fine-tune the physiological function of estrogen receptors, thereby bearing a direct impact on human health and disease.
雌激素受体在哺乳动物中由ERα和ERβ亚型组成，作为配体调节的转录因子，协调从性发育、生殖到代谢稳态等众多细胞功能。在此，我根据核受体领域的最新发现和新趋势，重新审视ERα与DNA及雌二醇结合的结构基础。本综述特别强调雌激素受体生理、环境和合成配体种类不断增加，其化学和结构多样性最终调节它们与雌激素反应基因启动子内同源DNA的相互作用。特别是，小分子配体对雌激素受体的调节是治疗包括乳腺癌、心血管疾病、骨质疏松症和肥胖症在内的多种人类疾病的重要治疗目标。总体而言，本文概述了一系列可微调雌激素受体生理功能的有机和无机小分子，从而对人类健康和疾病产生直接影响。
